This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Smoking induced endobronchial and oral cancers are leading causes of tobacco induced mortality. More accurate methods for diagnosis are needed to improve treatment and survival. We are developing-high resolution (near histological level) flexible fiberoptic endoscopic optical coherence tomographic methods for oral and airway cancer detection and monitoring. Optical coherence tomography (OCT) and optical Doppler tomography use interferometric broad-band coherent gating reflectance techniques to obtain high resolution structural and capillary flow dynamics at defined high resolution spatial locations even in highly scattering tissues like oral mucosa and airways. The 2-10 um OCT resolution capabilities enable us to begin investigation of non-invasive optical imaging of in-vivo tissue structure and microcirculation for diagnosis of oral and airway cancers. We propose to improve diagnosis and treatment of smoking induced airway and oral cancers by further development of flexible fiberoptic OCT/ODT for pulmonary and oral oncologic applications. Specific Aims: 1. To develop real-time flexible fiberoptic bronchoscopic methods for high-resolution simultaneous OCT/ODT evaluation of airway and oral tumors. 2. Evaluate these OCT/ODT capabilities for identifying oral cancers in live animal models and airway cancers in patients with smoking induced airway malignancy. 3. Assess the potential for combining low resolution in-vivo tumor fluorescence localization with OCT/ODT high resolution imaging to improve diagnostic yield and detection efficiency for oral and airway cancers, and to better understand functional optical markers for malignant transformation. 4. Develop methods for ultra-high resolution Ti:sapphire in-vivo OCT imaging.